Clinical Drug Experience Knowledgebase

Criteria

Inclusion Criteria:

Specimen collection screening

Karnofsky performance status (KPS) ≥ 60 at assessment prior to surgery
≥ 18 and ≤ 70 years of age
Subject has been diagnosed with GBM and has undergone resection surgery followed by standard brain RT + concurrent temozolomide and adjuvant temozolomide, and progression occurred. The foregoing progression is defined as when patients with primary GBM experience an image or clinical deterioration after receiving standard of care.
Contrast-enhanced MRI suspects recurrent GBM
Supratentorial tumor
Must voluntarily sign and date informed consent form for specimen acquisition and future use, for study screening, approved by an Independent Ethics Committee (IEC)/ Institutional Review Board (IRB), prior to the initiation of any study-specific procedures

Study screening

Karnofsky performance status (KPS) ≥ 60 at randomization
Submission of fresh tumor
Post-operation contrast-enhanced MRI scan must be done after surgical resection, with the intent for cyto-reduction ≥ 80% of the contrast-enhancing tumor mass
Histologically confirmed WHO grade IV glioma by pathology tissue screening
Subjects receiving bevacizumab as standard of care for given indication

Subject has adequate bone marrow, renal, and hepatic function prior to randomization as follow:

White blood cell (WBC) count ≥ 2,000/mm^3;
Absolute neutrophil count (ANC) ≥ 1,000/mm^3;
Platelets ≥ 100,000/mm^3;
Hemoglobin (Hgb) ≥ 8.0 g/dL (Note: The use of transfusion or other intervention to achieve Hgb ≥ 8.0 g/dL is acceptable.);
Blood Urea Nitrogen (BUN) < 30 mg/dL;
Creatinine < 2 mg/dL;
Renal function: calculated creatinine clearance ≥ 30 mL/min;
Hepatic function: Total bilirubin ≤ 3 times upper limit of normal (ULN), Aspartate Aminotransferase (AST) and Alanine Aminotransferase (ALT) ≤ 2 times ULN;
Prothrombin Time (PT) and activated partial thromboplastin time (PTT) ≤ 1.6 times ULN unless therapeutically warranted.
Subjects with recurrent GBM (Grade IV) are eligible for this protocol. An independent neuropathologist will review this diagnosis during the enrollment process
Must voluntarily sign and date informed consent form, for study participation, approved by an Independent Ethics Committee (IEC)/ Institutional Review Board (IRB), prior to the initiation of any study-specific procedures

Exclusion Criteria:

Specimen collection screening

Multifocal GBM
Prior invasive malignancy (except for non-melanomatous skin cancer; carcinoma in situ of breast, oral cavity or cervix) unless disease free for ≥ 2 years
Subject has used bevacizumab or immune checkpoint blockade to treat GBM
Lactating or pregnant female
Positive viral serology for HIV or syphilis at time of screening

Study screening

Subjects having a biopsy only at surgery or tumor cell insufficiency at preparation
Inability to undergo contrast-enhanced MRI scans
Subjects receiving investigational study drug for any indication or immunological-based treatment for any reason (Filgrastim may be used for prevention of severe neutropenia)
Inability to stop or decrease the use of corticosteroid doses to 4 mg/day prior to randomization
Tumor progression documented according to modified RANO criteria prior to randomization (approximately 5 weeks after surgery)

Severe, active comorbidity, defined as follow:

Subject with clinically defined Acquired Immune-Deficiency Syndrome (AIDS)-defining illness;
Subjects with acute hepatitis C or B infection;
Severe hepatic impairment (Child-Pugh category C or higher);
Electrocardiogram (ECG) with evidence of acute cardiac ischemia prior to randomization;
Transmural myocardial infarction or ischemia prior to enrollment;
Any other major medical illnesses or psychiatric impairments that in the Investigator's opinion will prevent administration or completion of protocol therapy
Subject used Gliadel wafer implant in surgery during screening process